Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
22868939
TITLE
Increased genetic vulnerability to smoking at CHRNA5 in early-onset smokers.
ABSTRACT
CONTEXT NlmCategory: BACKGROUND
Recent studies have shown an association between cigarettes per day (CPD) and a nonsynonymous single-nucleotide polymorphism in CHRNA5, rs16969968.
OBJECTIVE NlmCategory: OBJECTIVE
To determine whether the association between rs16969968 and smoking is modified by age at onset of regular smoking.
DATA SOURCES NlmCategory: METHODS
Primary data.
STUDY SELECTION NlmCategory: METHODS
Available genetic studies containing measures of CPD and the genotype of rs16969968 or its proxy.
DATA EXTRACTION NlmCategory: METHODS
Uniform statistical analysis scripts were run locally. Starting with 94,050 ever-smokers from 43 studies, we extracted the heavy smokers (CPD >20) and light smokers (CPD ≤10) with age-at-onset information, reducing the sample size to 33,348. Each study was stratified into early-onset smokers (age at onset ≤16 years) and late-onset smokers (age at onset >16 years), and a logistic regression of heavy vs light smoking with the rs16969968 genotype was computed for each stratum. Meta-analysis was performed within each age-at-onset stratum.
DATA SYNTHESIS NlmCategory: RESULTS
Individuals with 1 risk allele at rs16969968 who were early-onset smokers were significantly more likely to be heavy smokers in adulthood (odds ratio [OR] = 1.45; 95% CI, 1.36-1.55; n = 13,843) than were carriers of the risk allele who were late-onset smokers (OR = 1.27; 95% CI, 1.21-1.33, n = 19,505) (P = .01).
CONCLUSION NlmCategory: CONCLUSIONS
These results highlight an increased genetic vulnerability to smoking in early-onset smokers.
DATE PUBLISHED
2012 Aug
HISTORY
PUBSTATUS PUBSTATUSDATE
entrez 2012/08/08 06:00
pubmed 2012/08/08 06:00
medline 2012/10/19 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Hartz SM Hartz Sarah M SM Washington University School of Medicine, St Louis, Missouri, USA.
Short SE Short Susan E SE
Saccone NL Saccone Nancy L NL
Culverhouse R Culverhouse Robert R
Chen L Chen LiShiun L
Schwantes-An TH Schwantes-An Tae-Hwi TH
Coon H Coon Hilary H
Han Y Han Younghun Y
Stephens SH Stephens Sarah H SH
Sun J Sun Juzhong J
Chen X Chen Xiangning X
Ducci F Ducci Francesca F
Dueker N Dueker Nicole N
Franceschini N Franceschini Nora N
Frank J Frank Josef J
Geller F Geller Frank F
Gubjartsson D Gubjartsson Daniel D
Hansel NN Hansel Nadia N NN
Jiang C Jiang Chenhui C
Keskitalo-Vuokko K Keskitalo-Vuokko Kaisu K
Liu Z Liu Zhen Z
Lyytikäinen LP Lyytikäinen Leo-Pekka LP
Michel M Michel Martha M
Rawal R Rawal Rajesh R
Rosenberger A Rosenberger Albert A
Scheet P Scheet Paul P
Shaffer JR Shaffer John R JR
Teumer A Teumer Alexander A
Thompson JR Thompson John R JR
Vink JM Vink Jacqueline M JM
Vogelzangs N Vogelzangs Nicole N
Wenzlaff AS Wenzlaff Angela S AS
Wheeler W Wheeler William W
Xiao X Xiao Xiangjun X
Yang BZ Yang Bao-Zhu BZ
Aggen SH Aggen Steven H SH
Balmforth AJ Balmforth Anthony J AJ
Baumeister SE Baumeister Sebastian E SE
Beaty T Beaty Terri T
Bennett S Bennett Siiri S
Bergen AW Bergen Andrew W AW
Boyd HA Boyd Heather A HA
Broms U Broms Ulla U
Campbell H Campbell Harry H
Chatterjee N Chatterjee Nilanjan N
Chen J Chen Jingchun J
Cheng YC Cheng Yu-Ching YC
Cichon S Cichon Sven S
Couper D Couper David D
Cucca F Cucca Francesco F
Dick DM Dick Danielle M DM
Foroud T Foroud Tatiana T
Furberg H Furberg Helena H
Giegling I Giegling Ina I
Gu F Gu Fangyi F
Hall AS Hall Alistair S AS
Hällfors J Hällfors Jenni J
Han S Han Shizhong S
Hartmann AM Hartmann Annette M AM
Hayward C Hayward Caroline C
Heikkilä K Heikkilä Kauko K
Hewitt JK Hewitt John K JK
Hottenga JJ Hottenga Jouke Jan JJ
Jensen MK Jensen Majken K MK
Jousilahti P Jousilahti Pekka P
Kaakinen M Kaakinen Marika M
Kittner SJ Kittner Steven J SJ
Konte B Konte Bettina B
Korhonen T Korhonen Tellervo T
Landi MT Landi Maria-Teresa MT
Laatikainen T Laatikainen Tiina T
Leppert M Leppert Mark M
Levy SM Levy Steven M SM
Mathias RA Mathias Rasika A RA
McNeil DW McNeil Daniel W DW
Medland SE Medland Sarah E SE
Montgomery GW Montgomery Grant W GW
Muley T Muley Thomas T
Murray T Murray Tanda T
Nauck M Nauck Matthias M
North K North Kari K
Pergadia M Pergadia Michele M
Polasek O Polasek Ozren O
Ramos EM Ramos Erin M EM
Ripatti S Ripatti Samuli S
Risch A Risch Angela A
Ruczinski I Ruczinski Ingo I
Rudan I Rudan Igor I
Salomaa V Salomaa Veikko V
Schlessinger D Schlessinger David D
Styrkársdóttir U Styrkársdóttir Unnur U
Terracciano A Terracciano Antonio A
Uda M Uda Manuela M
Willemsen G Willemsen Gonneke G
Wu X Wu Xifeng X
Abecasis G Abecasis Goncalo G
Barnes K Barnes Kathleen K
Bickeböller H Bickeböller Heike H
Boerwinkle E Boerwinkle Eric E
Boomsma DI Boomsma Dorret I DI
Caporaso N Caporaso Neil N
Duan J Duan Jubao J
Edenberg HJ Edenberg Howard J HJ
Francks C Francks Clyde C
Gejman PV Gejman Pablo V PV
Gelernter J Gelernter Joel J
Grabe HJ Grabe Hans Jörgen HJ
Hops H Hops Hyman H
Jarvelin MR Jarvelin Marjo-Riitta MR
Viikari J Viikari Jorma J
Kähönen M Kähönen Mika M
Kendler KS Kendler Kenneth S KS
Lehtimäki T Lehtimäki Terho T
Levinson DF Levinson Douglas F DF
Marazita ML Marazita Mary L ML
Marchini J Marchini Jonathan J
Melbye M Melbye Mads M
Mitchell BD Mitchell Braxton D BD
Murray JC Murray Jeffrey C JC
Nöthen MM Nöthen Markus M MM
Penninx BW Penninx Brenda W BW
Raitakari O Raitakari Olli O
Rietschel M Rietschel Marcella M
Rujescu D Rujescu Dan D
Samani NJ Samani Nilesh J NJ
Sanders AR Sanders Alan R AR
Schwartz AG Schwartz Ann G AG
Shete S Shete Sanjay S
Shi J Shi Jianxin J
Spitz M Spitz Margaret M
Stefansson K Stefansson Kari K
Swan GE Swan Gary E GE
Thorgeirsson T Thorgeirsson Thorgeir T
Völzke H Völzke Henry H
Wei Q Wei Qingyi Q
Wichmann HE Wichmann H-Erich HE
Amos CI Amos Christopher I CI
Breslau N Breslau Naomi N
Cannon DS Cannon Dale S DS
Ehringer M Ehringer Marissa M
Grucza R Grucza Richard R
Hatsukami D Hatsukami Dorothy D
Heath A Heath Andrew A
Johnson EO Johnson Eric O EO
Kaprio J Kaprio Jaakko J
Madden P Madden Pamela P
Martin NG Martin Nicholas G NG
Stevens VL Stevens Victoria L VL
Stitzel JA Stitzel Jerry A JA
Weiss RB Weiss Robert B RB
Kraft P Kraft Peter P
Bierut LJ Bierut Laura J LJ
INVESTIGATORS
JOURNAL
VOLUME: 69
ISSUE: 8
TITLE: Archives of general psychiatry
ISOABBREVIATION: Arch. Gen. Psychiatry
YEAR: 2012
MONTH: Aug
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1538-3636
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Arch Gen Psychiatry
COUNTRY: United States
ISSNLINKING: 0003-990X
NLMUNIQUEID: 0372435
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
090532 Wellcome Trust United Kingdom
DA019951 NIDA NIH HHS United States
DA12854 NIDA NIH HHS United States
HHSN268200782096C PHS HHS United States
K01 DA019498 NIDA NIH HHS United States
K01 DA024758 NIDA NIH HHS United States
K01DA19498 NIDA NIH HHS United States
K01DA24758 NIDA NIH HHS United States
K02 AA018755 NIAAA NIH HHS United States
K02 AA018755 NIAAA NIH HHS United States
K02 DA021237 NIDA NIH HHS United States
K02DA021237 NIDA NIH HHS United States
K05 AA017688 NIAAA NIH HHS United States
K07 CA118412 NCI NIH HHS United States
K07 CA118412 NCI NIH HHS United States
K08 DA019951 NIDA NIH HHS United States
K08 DA030398 NIDA NIH HHS United States
K08 DA032680 NIDA NIH HHS United States
KL2 RR024994 NCRR NIH HHS United States
KL2 TR000450 NCATS NIH HHS United States
MH46289 NIMH NIH HHS United States
MH46318 NIMH NIH HHS United States
N01 AG012100 NIA NIH HHS United States
N01 HR046002 NHLBI NIH HHS United States
N01-AG-1-2109 NIA NIH HHS United States
N01-HR-46002 NHLBI NIH HHS United States
N01-PC35145 NCI NIH HHS United States
N01-PC35146 NCI NIH HHS United States
N01PC35145 NCI NIH HHS United States
P01 CA089392 NCI NIH HHS United States
P01 CA089392 NCI NIH HHS United States
R01 AA011330 NIAAA NIH HHS United States
R01 AA017535 NIAAA NIH HHS United States
R01 AA017535 NIAAA NIH HHS United States
R01 AA11330 NIAAA NIH HHS United States
R01 CA060691 NCI NIH HHS United States
R01 DA003706 NIDA NIH HHS United States
R01 DA012690 NIDA NIH HHS United States
R01 DA012849 NIDA NIH HHS United States
R01 DA012854 NIDA NIH HHS United States
R01 DA017932 NIDA NIH HHS United States
R01 DA017932 NIDA NIH HHS United States
R01 DA025888 NIDA NIH HHS United States
R01 DA026911 NIDA NIH HHS United States
R01 DA03706 NIDA NIH HHS United States
R01 DA12690 NIDA NIH HHS United States
R01 DA12849 NIDA NIH HHS United States
R01 DE012101 NIDCR NIH HHS United States
R01 HL089651 NHLBI NIH HHS United States
R01 MH059565 NIMH NIH HHS United States
R01 MH059566 NIMH NIH HHS United States
R01 MH059571 NIMH NIH HHS United States
R01 MH059586 NIMH NIH HHS United States
R01 MH059587 NIMH NIH HHS United States
R01 MH059588 NIMH NIH HHS United States
R01 MH060870 NIMH NIH HHS United States
R01 MH060879 NIMH NIH HHS United States
R01 MH067257 NIMH NIH HHS United States
R01 MH081800 NIMH NIH HHS United States
R01 MH59565 NIMH NIH HHS United States
R01 MH59566 NIMH NIH HHS United States
R01 MH59571 NIMH NIH HHS United States
R01 MH59586 NIMH NIH HHS United States
R01 MH59587 NIMH NIH HHS United States
R01 MH59588 NIMH NIH HHS United States
R01 MH60870 NIMH NIH HHS United States
R01 MH60879 NIMH NIH HHS United States
R01 MH61675 NIMH NIH HHS United States
R01 MH67257 NIMH NIH HHS United States
R01 MH81800 NIMH NIH HHS United States
R01 NS045012 NINDS NIH HHS United States
R01CA060691 NCI NIH HHS United States
R01DA026911 NIDA NIH HHS United States
R01DA25888 NIDA NIH HHS United States
R01HL089651-01 NHLBI NIH HHS United States
R01NS45012 NINDS NIH HHS United States
R03 AG035146 NIA NIH HHS United States
R21 DA027070 NIDA NIH HHS United States
R21 DA033827 NIDA NIH HHS United States
R21DA027070 NIDA NIH HHS United States
R21DA033827 NIDA NIH HHS United States
R24 HD041020 NICHD NIH HHS United States
T32 MH014677 NIMH NIH HHS United States
T32 MH014677 NIMH NIH HHS United States
TL1 RR024995 NCRR NIH HHS United States
TL1 TR000449 NCATS NIH HHS United States
U01 DA020830 NIDA NIH HHS United States
U01 DE018903 NIDCR NIH HHS United States
U01 HG004436 NHGRI NIH HHS United States
U01 HG004436 NHGRI NIH HHS United States
U01 HG004438 NHGRI NIH HHS United States
U01 HG004446 NHGRI NIH HHS United States
U01 HG004738 NHGRI NIH HHS United States
U01 MH046276 NIMH NIH HHS United States
U01 MH046276-08 NIMH NIH HHS United States
U01 MH046289-08 NIMH NIH HHS United States
U01 MH046318 NIMH NIH HHS United States
U01 MH046318-08 NIMH NIH HHS United States
U01 MH079469 NIMH NIH HHS United States
U01 MH079470 NIMH NIH HHS United States
U01 MH46276 NIMH NIH HHS United States
U01 MH79469 NIMH NIH HHS United States
U01 MH79470 NIMH NIH HHS United States
U01 NS069208 NINDS NIH HHS United States
U01 NS069208 NINDS NIH HHS United States
U01-DE018903 NIDCR NIH HHS United States
U01DA02830 NIDA NIH HHS United States
U01HG004438 NHGRI NIH HHS United States
U01HG004446 NHGRI NIH HHS United States
U01HG004738 NHGRI NIH HHS United States
U10 AA008401 NIAAA NIH HHS United States
U10 AA008401 NIAAA NIH HHS United States
U19 CA148127 NCI NIH HHS United States
U54 RR020278 NCRR NIH HHS United States
U54 RR020278 NCRR NIH HHS United States
UL1 RR024992 NCRR NIH HHS United States
UL1 TR000448 NCATS NIH HHS United States
UL1RR024992 NCRR NIH HHS United States
Z99 AG999999 Intramural NIH HHS United States
ZIA AG000196-03 Intramural NIH HHS United States
ZIA AG000196-04 Intramural NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adolescent
Adolescent Development drug effects
Adult drug effects
Age of Onset drug effects
Europe epidemiology
Female epidemiology
Gene-Environment Interaction epidemiology
Genetic Association Studies epidemiology
Genetic Predisposition to Disease epidemiology
Humans epidemiology
Male epidemiology
Nerve Tissue Proteins genetics
Nicotine pharmacology
Polymorphism, Single Nucleotide pharmacology
Receptors, Nicotinic genetics
Severity of Illness Index genetics
Smoking genetics
Tobacco Use Disorder psychology
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 CHRNA5 protein, human
0 Nerve Tissue Proteins
0 Receptors, Nicotinic
6M3C89ZY6R Nicotine
OTHER ID's
OTHERID SOURCE
NIHMS400549 NLM
PMC3482121 NLM